Structure-based study of antiamyloidogenic cyclic d,l-α-peptides

Marina Chemerovski-Glikman, Michal Richman, Shai Rahimipour

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Protein misfolding and aggregation are the hallmarks of many devastating diseases. We have previously shown that cyclic d,l-α-peptide CP-2 reacts and stabilizes less toxic forms of amyloid β (Aβ), and protects the cells from Aβ-induced toxicity. Here, we performed extensive structure-based studies on CP-2 to elucidate the contribution of each residue to the total antiamyloidogenic activity and determine the interactions that are involved between CP-2 and Aβ. We showed that the hydrophobicity of CP-2 analogs correlates with their antiamyloidogenic potency, however, aromatic interactions are even more important for this activity. The antiamyloidogenic activity of CP-2 analogs also correlates with their ability to self-assemble, as shown by the critical micelle concentration measurements. The cell survival studies performed on rat pheochromocytoma PC-12 cells suggest that incorporation of an additional aromatic residue to the CP-2's sequence increases its protective effect against Aβ42-induced toxicity.

Original languageEnglish
Pages (from-to)7639-7644
Number of pages6
JournalTetrahedron
Volume70
Issue number42
DOIs
StatePublished - 21 Oct 2014

Bibliographical note

Publisher Copyright:
© 2014 Elsevier Ltd. All rights reserved.

Keywords

  • Alzheimer's disease
  • Amyloid β
  • Antiamyloidogenic activity
  • Conformational mimics
  • Cyclic d,l-α-peptide

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